This invention relates to iron-binding polymers, particularly polymers administered orally to decrease the absorption of dietary iron from the gastrointestinal tract.
Reduced uptake of dietary iron is clinically important in several related metabolic disorders. In patients with hemachromatosis too much dietary iron is absorbed and patients experience iron overload. Genetic hemachromatosis is due to a somatic gene mutation. While tissue damage is greatest in individuals who are homozygous for the defective gene, reduction of iron uptake is also desirable in patients who are heterozygous for the implicated mutation (Finch et al., N. Engl. J. Med., 306:1520, 1982). Acquired hemachromatosis includes conditions characterized by tissue injury associated with iron overload, where disease processes other than genetic mutations cause the exacerbated iron uptake. Examples of such diseases include iron-loading anemias, such as thalassemia and sideroblastic anemia, as well as certain types of liver dysfunction (Finch et al., N. Engl. J. Med., 306: 1520, 1982). The massive deposits of iron in body tissues cause similar organ failure in both genetic and acquired hemachromatosis.
Until recently, relatively high iron levels were considered desirable in all individuals. However, increased rates of heart disease are now known to be associated with elevated serum ferritin levels (an indicator of the body burden of iron). In the heterozygous state of hemachromatosis, for example, the degree of iron overload is not sufficient to lead to the traditional symptoms of overload, including abdominal pain, hepatomegaly, diabetes, impotence, and gray pigmentation of the skin. The iron overload may be sufficient, however, to lead to increased probability of heart disease such as congestive heart failure.
A typical adult man has 4-6 g of iron in his body, and absorbs approximately 1 mg of the 10-20 mg of iron available from his daily diet. Iron is absorbed in two basic forms, free iron and heme-bound iron. Free iron can be in either the ferrous (Fe.sup.+2) or ferric (Fe.sup.+3) forms, and can be complexed to various organic and inorganic dietary ingredients (such as phosphate, phytate and citrate). The two forms of free iron are absorbed equally well provided that they both remain in an ionized form, and not in the easily formed and insoluble hydroxides. A typical adult diet contains approximately 1.6 mg of heme-bound iron and 13 mg of free iron. Heme-bound iron, while present in smaller amounts in the diet than free iron, is more readily absorbed than free iron. Approximately 23% of heme-bound iron is available for absorption, while the absorbable fraction of dietary free iron ranges from 3-8%, depending on the other constituents of the diet. The result of these factors is that both heme-bound and free iron contribute significantly to dietary iron uptake.
Iron is absorbed primarily in the proximal segments of the small intestine. It is absorbed by the mucosal cells, processed into appropriate forms, and released into the plasma.